We have used in situ hybridization and immunocytochemistry to map the cellular pattern of distribution for IGF-I, the IGF-I receptor and a number of specific IGF binding proteins (IGFBPs) during the brain's development and in the brain's response to injury. The distinctive cellular distribution and timing of IGF- I and the IGF-I receptor expression during brain development strongly suggest a role for IGF-I in the myelination of a specific class of central projection neurons. In support of this view, our preliminary studies in a model of experimental demyelination- remyelination show a resurgence of IGF-I expression during the remyelinating process. Also, we have found that both IGF-I and IGF-II are strongly expressed in the setting of cerebral ischemia, and are currently investigating their roles in this critical situation. We have also studied IGF system expression in the kidney during normal development and after hypophysectomy and growth hormone treatment. These studies suggest that IGF-II is involved in renal angiogenesis and that IGFBP-2 may be instrumental in the clearance of circulating IGFs into the urine. IGF-I, IGFBP-1 and the IGF-I receptor are found colocalized in a specific region of the mature kidney - a region critical for dilution of the tubular fluid. Renal expression of these factors was found to be regulated by growth hormone released from the pituitary. It thus appears that the intrarenal IGF system may constitute a physiological mechanism whereby the kidney, under the influence of the pituitary, adapts to changing fuel consumption and the associated changes in metabolic and water loads.